Alveolar-arterial PO2 Gradient Research Articles

A New, Noninvasive Method of Measuring Pulmonary Gas Exchange: Results in Normal Subjects and Patients with Lung Disease

MethodsThe person breathes through a device that continually measures and displays the inspired and expired PO2 and PCO2. An oximeter is worn, and the arterial PO2 is calculated from the SpO2 and the oxygen dissociation curve, using the end–tidal PCO2 to account for the effect of PCO2 on the oxygen affinity of hemoglobin. The PO2 difference between the end‐tidal gas and the calculated arterial value is called the Oxygen Deficit. Since the calculation is only accurate when the arterial oxygen saturations are 94% or less, the normal subjects breathed 12.5% oxygen.ResultsStudies were made on 17 patients with a variety of pulmonary diseases who were attending an outpatient clinic. The mean oxygen deficit was 48.7 mm Hg, SE 3.1. This can be contrasted with a mean oxygen deficit of 4.0 mm Hg, SE 0.91 in a group of 30 normal subjects who were previously studied. The p value for the difference between the two groups was < 0.0001. Within the normal subjects, the mean oxygen deficit for the 19 younger participants (ages 22–31) was 2.02 mm Hg, SE 0.84 while that in the 11 older participants (ages 47–88) was 7.53 mm Hg, SE 1.55. The p value for the difference between the young and old groups was 0.0015. The mean oxygen deficit in younger normal subjects is remarkably small. This implies that there is very little difference between the calculated arterial PO2 and the alveolar PO2, consistent with little impairment of gas exchange. However, the mean oxygen deficit in older normal subjects is significantly higher consistent with the increased Alveolar‐arterial (A‐a) PO2 gradient with age, which has been well documented in the literature. Analysis of the factors determining the magnitude of the oxygen deficit showed that the end–tidal PO2 was the most important factor, followed by the end–tidal PCO2, and the calculated arterial PO2. Interestingly the SpO2 had a minor influence in spite of the fact that the oximeter reading is frequently used to guide therapy. The analysis emphasizes the value of measuring the composition of alveolar gas in determining ventilation‐perfusion ratio inequality. Remarkably, this factor is largely ignored in the classical index of impaired pulmonary gas exchange using the ideal alveolar PO2 to calculate the A‐a O2 gradient. We argue that ignoring the actual alveolar value gives an incomplete picture of gas exchange in the lungs because the traditional index is heavily biased by lung units with low ventilation‐perfusion ratios. Therefore, by using the new index of oxygen deficit, we derive a more comprehensive measurement of gas exchange in the lungs.Support or Funding InformationSupported by MediPines IncThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Monitoring Oxygen Status.

Although part of a common "blood gas" test panel with pH and pCO2, the pO2, %O2Hb, and related parameters are independently used to detect and monitor oxygen deficits from a variety of causes. Measurement of blood gases and cooximetry may be done by laboratory analyzers, point of care testing, noninvasive pulse oximetry, and transcutaneous blood gases. The specimen type and mode of monitoring oxygenation that are chosen may be based on a combination of urgency, practicality, clinical need, and therapeutic objectives. Because oxygen concentrations in blood are extremely labile, there are several highly important preanalytical practices necessary to prevent errors in oxygen and cooximetry results. Effective utilization of oxygen requires binding by hemoglobin in the lungs, transport in the blood, and release to tissues, where cellular respiration occurs. Hydrogen ion (pH), CO2, temperature, and 2,3-DPG all play important roles in these processes. Additional measurements and calculations are often used to interpret and locate the cause and source of an oxygen deficit. These include the Hb concentration, Alveolar-arterial pO2 gradient, pO2:FIO2 ratio, oxygenation index, O2 content and O2 delivery, and pulmonary dead space and intrapulmonary shunting. The causes of hypoxemia will be covered and, to illustrate how the oxygen parameters are used clinically in the diagnosis and management of patients with abnormal oxygenation, two clinical cases will be presented and described.

Role of the Chemokine Receptors CXCR3 and CCR4 in Human Pulmonary Fibrosis

The chemokine receptors CXCR3 and CCR4 have recently been described as playing a pivotal role in the mouse model of bleomycin-induced fibrosis. To evaluate the role of these receptors in human idiopathic pulmonary fibrosis (IPF). We studied 57 patients: 18 with IPF, 17 with non-IPF (nIPF), 12 with sarcoidosis, and 10 healthy control subjects. We evaluated the expression of CXCR3 and CCR4 in blood and bronchoalveolar lavage (BAL) T lymphocytes by flow cytometry and the chemokine CXCL10, CXCL11 and CCL17 BAL concentration by singular immunoassay. Patients with IPF had a significantly lower CXCR3 and a higher CCR4 expression on BAL CD4 T cells compared with the other groups. Among patients with IPF, those treated with corticosteroids exhibited higher CXCR3 and lower CCR4 expression compared with untreated patients. CXCR3 expression correlated with BAL lymphocytes and CCR4 with BAL neutrophils and eosinophils. CXCL10 levels correlated with the expression of CXCR3 on BAL CD4 cells. CXCL11 was undetectable in almost all patients, whereas CCL17 was primarily detectable in patients with IPF. The percentage of BAL CCR4CD4 cells negatively correlated with DL(CO). The changes in the total lung capacity, VC, and of the alveolar-arterial PO2 gradient in patients with IPF and those with nIPF 6 to 12 mo after the first evaluation were associated with CD4CXCR3 percentage on BAL cells. We found an imbalance in CXCR3/CCR4 expression on BAL CD4 lymphocytes and reduced CXCL10 BAL levels in patients with IPF, suggesting a pivotal role of these molecules in IPF.

The effect of moderate hypovolemia on cardiopulmonary function in dogs

AbstractObjective: To collate canine cardiopulmonary measurements from previously published and unpublished studies in instrumented, unsedated, normovolemic and moderately hypovolemic dogs.Design: Collation of data obtained from original investigations in our research laboratory.Setting: Research laboratory, School of Veterinary Medicine.Subjects: Sixty‐eight dogs.Interventions: Subjects were percutaneously instrumented with an arterial catheter and a thermodilution cardiac output catheter. A femoral artery catheter was percutaneously placed for blood removal.Measurements and main results: Body weight, arterial and mixed‐venous pH and blood gases, arterial, pulmonary arterial, pulmonary artery occlusion, and central venous blood pressure, cardiac output, and core body temperature were measured. Body surface area, bicarbonate concentration, standard base excess, cardiac index (CI), stroke volume, systemic and pulmonary vascular resistance, left and right ventricular work and stroke work indices, left and right rate‐pressure product, alveolar PO2, alveolar–arterial PO2 gradient, arterial and mixed‐venous and pulmonary capillary oxygen content, oxygen delivery, oxygen consumption, oxygen extraction, venous admixture, arterial and venous blood carbon dioxide content, arterial–venous carbon dioxide gradient, carbon dioxide production were calculated.In 68 dogs, hypovolemia sufficient to decrease mean arterial blood pressure (ABPm) to an average of 62 mmHg, was associated with the following changes: arterial partial pressure of carbon dioxide (PaCO2) decreased from 40.0 to 32.9 mmHg; arterial base deficit (BDa) increased from −2.2 to −6.3 mEq/L; lactate increased from 0.85 to 10.7 mm/L, and arterial pH (pHa) did not change. Arterial partial pressure of oxygen (PaO2) increased from 100.5 to 108.3 mmHg while mixed‐venous PO2 (PmvO2) decreased from 49.1 to 34.1 mmHg. Arterial and mixed‐venous oxygen content (CaO2 and CmvO2) decreased from 17.5 to 16.5 and 13.8 to 9.6 mL/dL, respectively. The alveolar–arterial PO2 gradient (A‐a PO2) increased from 5.5 to 8.9 mmHg while venous admixture decreased from 2.9% to 1.4%. The ABPm decreased from 100 to 62 mmHg; pulmonary arterial pressure (PAPm) decreased from 13.6 to 6.4 mmHg; and pulmonary arterial occlusion pressure (PAOP) decreased from 4.9 to 0.1 mmHg. CI decreased from 4.31 to 2.02 L/min/m2. Systemic and pulmonary vascular resistance (SVRI and PVRI) increased from 1962 to 2753 and 189 to 269 dyn s/cm5, respectively. Oxygen delivery (DO2) decreased from 787 to 340 mL/min/m2 while oxygen consumption (VO2) decreased from 172 to 141 mL/min/m2. Oxygen extraction increased from 20.9% to 42.3%.Conclusions: Moderate hypovolemia caused CI and oxygen delivery to decrease to 47% and 42% of baseline. Oxygen extraction, however, doubled and, therefore, oxygen consumption decreased only to 82% of baseline.

Modeling diffusion limitation of gas exchange in lungs containing perfluorocarbon.

We reported changes in alveolar-arterial PO2 gradient, ventilation-perfusion heterogeneity, and arterial-alveolar PCO2 gradient during partial liquid ventilation (PLV) in healthy piglets (E. A. Mates, P. Tarczy-Hornoch, J. Hildebrandt, J. C. Jackson, and M. P. Hlastala. In: Oxygen Transport to Tissue XVII, edited by C. Ince. New York: Plenum, 1996, vol. 388, p. 585-597). Here we develop two mathematical models to predict transient and steady-state (SS) gas exchange conditions during PLV and to estimate the contribution of diffusion limitation to SS arterial-alveolar differences. In the simplest model, perfluorocarbon is represented as a uniform flat stirred layer and, in a more complex model, as an unstirred spherical layer in a ventilated terminal alveolar sac. Time-dependent solutions of both models show that SS is established for various inert and respiratory gases within 5-150 s. In fluid-filled unventilated terminal units, all times to SS increased sometimes by hours, e.g., SF6 exceeded 4 h. SS solutions for the ventilated spherical model predicted minor end-capillary disequilibrium of inert gases and significant disequilibrium of respiratory gases, which could explain a large portion of the arterial-alveolar PCO2 gradient measured during PLV (14). We conclude that, during PLV, diffusion gradients for gases are generally small, except for CO2.

Effect of prolonged heavy exercise on pulmonary gas exchange in horses.

During short-term maximal exercise, horses have impaired pulmonary gas exchange, manifested by diffusion limitation and arterial hypoxemia, without marked ventilation-perfusion (VA/Q) inequality. Whether gas exchange deteriorates progressively during prolonged submaximal exercise has not been investigated. Six thoroughbred horses performed treadmill exercise at approximately 60% of maximal oxygen uptake until exhaustion (28-39 min). Multiple inert gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained at rest and 5-min intervals during exercise. Oxygen uptake, cardiac output, and alveolar-arterial PO2 gradient were unchanged after the first 5 min of exercise. Alveolar ventilation increased progressively during exercise, from increased tidal volume and respiratory frequency, resulting in an increase in arterial PO2 and decrease in arterial PCO2. At rest there was minimal VA/Q inequality, log SD of the perfusion distribution (log SDQ) = 0.20. This doubled by 5 min of exercise (log SDQ = 0.40) but did not increase further. There was no evidence of alveolar-end-capillary diffusion limitation during exercise. However, there was evidence for gas-phase diffusion limitation at all time points, and enflurane was preferentially overretained. Horses maintain excellent pulmonary gas exchange during exhaustive, submaximal exercise. Although VA/Q inequality is greater than at rest, it is less than observed in most mammals and the effect on gas exchange is minimal.

Changes in lung function and pulmonary capillary permeability after cardiopulmonary bypass.

To assess the possibility that changes in lung function following cardiopulmonary bypass are associated with increased pulmonary capillary permeability. A prospective, descriptive study. Adult cardiothoracic ICU in a post-graduate teaching hospital. Ten sequential patients undergoing cardiac surgery requiring cardiopulmonary bypass. Arterial blood gas tensions, helium dilution end-expiratory lung volume, and carbon monoxide transfer were measured by a rebreathing technique preoperatively and 2 hrs postoperatively. Lung extravascular protein accumulation index was measured by a double-isotope technique 2 hrs postoperatively and in a group of normal controls. Mean +/- SEM alveolar-arterial PO2 gradient increased from 77 +/- 14 torr (10.3 +/- 1.8 kPa) to 138 +/- 24 torr (18.5 +/- 3.2 kPa) (p less than .01). Functional residual capacity decreased by 20.2 +/- 5.6% (p less than .01). Carbon monoxide transfer decreased by 26.7 +/- 5.3% (p less than .01) for the lung as a whole and by 17.9 +/- 3.2% (p less than .01) per liter of accessible gas volume. Protein accumulation index ranged from 0.03 to 3.2 x 10(-3) (median 0.6) postoperatively (median for normal subjects 0.4; p less than .05), although only one patient had a value indicative of clinically important endothelial injury. Cardiac surgery involving cardiopulmonary bypass results in a deterioration in lung function characterized by a loss of lung volume, a reduction in carbon monoxide transfer, and an increase in the alveolar-arterial PO2 gradient. These changes do not appear to be mediated by an increase in pulmonary endothelial permeability.

Aerosolized Pseudomonas elastase and lung fluid balance in anesthetized sheep.

The role of the lung epithelium in lung fluid balance was studied by ventilating anesthetized sheep with an aerosol of 20 mg of elastase from Pseudomonas aeruginosa (Ps. elastase) to increase lung epithelial permeability without affecting lung endothelial permeability or lung vascular pressures. Ps. elastase had no effect on the lung vascular pressures, the alveolar-arterial PO2 gradient (A-aPO2), the flow or protein concentration of the lung lymph, or the postmortem water volume of the lungs. The morphological alveolar flooding score in these sheep was 2.5 times the control level, but this was only marginally significant. Elevation of the left atrial pressure by 20 cmH2O alone increased the postmortem lung water volume but had no effect on A-aPO2, the alveolar flooding score, or the lung epithelial permeability assessed by the clearance of 99mTc-labeled human serum albumin. Addition of aerosolized Ps. elastase to these sheep had no effect on the total lung water volume, but it caused a redistribution of water into the air spaces, as evidenced by significant increases in the alveolar flooding score and A-aPO2 (P less than 0.01). Elevation of the left atrial pressure by 40 cmH2O without elastase caused the same response as elevation of the left atrial pressure by 20 cmH2O with elastase, except the higher pressure caused a greater increase in the total lung water volume. We conclude that alteration of the integrity of the lung epithelium with aerosolized Ps. elastase causes a redistribution of lung water into the alveoli without affecting the total lung water volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway occlusion pressure (P0.1)-a useful predictor for the weaning outcome in patients with acute respiratory failure-.

Twenty-five patients who required mechanical ventilatory support (MVS) after major surgery or severe burns were studied to determine whether airway occlusion pressure (P(0.1)) is a clinically useful indicator to predict the success or failure of the weaning trial. A total of 33 weaning trials were attempted on these patients. Of the 33 trials, 24 were followed by successful weaning and 9 by failure. Although the success group, when compared with the failure group, had a lower respiratory rate ( P << 0.001), a lower minute ventilation ( P << 0.001), a higher maximal voluntary ventilation to minute ventilation ratio ( P << 0.01) and a higher forced vital capacity ( P << 0.05), no threshold values separated the success from the failure group. The alveolar-arterial P(O)(2) gradient, with an F i(O)(2) of 1.0, in weaning success and failure showed no statistical difference. In contrast, all patients in the success group had a P(0.1) of less than 3.5 cmH(2)O and those in the failure group had a P(0.1) of greater than 3.5 cmH(2)O ( P << 0.001). We conclude that P(0.1) is a clinically superior indicator for discontinuing MVS in patients with acute respiratory failure.

Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep.

Recombinant interleukin 2 (rIL-2) administration, a new form of therapy for patients with far-advanced cancer, is associated with a "third space" syndrome, i.e., pulmonary edema, respiratory distress, and hypoxemia, which limits the dose and duration of treatment. To extend our knowledge regarding this toxicity, we established a sheep chronic lung lymph fistula model and measured hemodynamics, arterial blood gases, caudal mediastinal (lung) lymph flow (QL), and blood and lung lymph cellular changes before, during, and after (recovery) a 3-day continuous rIL-2 infusion (9 x 10(5) U/kg). Moderate systemic hypotension, mild pulmonary hypertension, and an increase in alveolar-arterial PO2 gradient was present on day 3 of rIL-2 infusion. QL increased from a base line of 1.9 +/- 0.2 to a maximum of 4.3 +/- 1.1 ml/15 min on day 3 of rIL-2 infusion. At no time was there a change in lymph-to-plasma protein ratio. The leukocyte count increased significantly to 16.1 +/- 4.5 x 10(3) cells/mm3 at recovery day 1. The percentage of blood lymphocytes decreased significantly by day 1 of rIL-2 infusion, returned to base-line levels on day 3, and significantly increased on day 2 of recovery. Lung lymph lymphocytes decreased significantly on days 1 and 2 of rIL-2 infusion. There was a shift in their size; i.e., their area increased from 32 +/- 7 to 57 +/- 19 micron 2 (P less than 0.05) by day 2 of rIL-2 infusion. By day 1 of recovery, lung lymph lymphocyte counts increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of improvement in pulmonary gas exchange during growth in awake piglets.

Previous studies have shown a lower arterial PO2 (PaO2) in infants and young animals than in adults. To investigate the mechanism of this impairment of gas exchange we studied 13 piglets from 12 to 65 days of age. Two days after instrumentation we measured the distribution of ventilation-perfusion ratios (VA/Q) by use of the multiple inert gas technique on awake animals. We showed that PaO2 is lower in young animals, increasing from 72 +/- 11.5 Torr before 2 wk to 102 Torr at 2 mo. This hypoxemia is due to an enlarged alveolar-arterial O2 pressure difference that significantly decreases with age. This impairment in gas exchange is not due to shunting (0.6 +/- 1.3%). Mean dead space (36 +/- 11%) was not related to age. Mean modes of perfusion and ventilation did not differ significantly between age groups. However, the dispersion of perfusion as expressed by its logSD decreased significantly with age, whereas dispersion of ventilation remained constant. Furthermore, in the young animals only, a significant difference was evidenced between measured alveolar-arterial PO2 gradient and the value predicted by the inert gas model. We therefore conclude that the impairment of gas exchange in piglets is due to two mechanisms: VA/Q mismatch and diffusion limitation for O2.

Correlation of Bronchoalveolar Lavage Cell Populations with Clinical Severity of Pneumocystis carinii Pneumonia

We correlated bronchoalveolar lavage (BAL) cell populations with clinical course and outcome in 19 patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome. Twelve patients demonstrated an elevated (greater than or equal to 5 percent) BAL combined neutrophil and eosinophil count, which correlated with the magnitude of the alveolar-arterial PO2 gradient. Patients with elevated BAL granulocytes also had significantly higher serum lactate dehydrogenase levels. Three of the four patients who died had the highest percentage of neutrophil counts observed in lavage fluid. Although no patient was thought to have a concurrent bacterial infection, potential pathogens were cultured from the sputum of patients with the most elevated neutrophil counts. Whether BAL granulocytes reflect an inflammatory process analogous to the adult respiratory distress syndrome or signify concomitant bacterial infection remains to be determined. We conclude that BAL granulocytes are associated with more severe respiratory compromise in patients with Pneumocystis carinii pneumonia.

Sequential cardiopulmonary changes after oleic-acid injury in dogs.

Oleic acid (OA) administered to experimental animals increases pulmonary vascular permeability and produces a condition that pathophysiologically resembles adult respiratory distress syndrome (ARDS) in humans. The present study examined the sequence of cardiorespiratory changes after OA infusion and their similarity to ARDS. After a baseline period, mechanically ventilated and anesthetized dogs were administered 0.18 ml/kg body weight OA into the pulmonary artery while hemodynamic and respiratory changes were monitored. After OA infusion, cardiac output fell by 39%, paralleling a 26% decrease in heart rate. Pulmonary vascular resistance (PVR) increased over 200% without a change in pulmonary capillary wedge pressure and initially without an increase in pulmonary artery pressure (PAP). Within 30 min after OA infusion, dynamic pulmonary compliance (Cdyn) was reduced 32% from baseline values, with a coincident increase in the alveolar-arterial PO2 gradient (P[A-a]O2) but without a significant change in the pulmonary shunt fraction (Qsp/Qt). This was followed in 30 min by a further 27% decrease in Cdyn, with a Qsp/Qt in excess of 50%. Both the hematocrit and hemoglobin concentration increased progressively after OA infusion, without a change in plasma protein concentration. The results suggest that the sequence of cardiopulmonary changes after OA injury are initially marked by a decrease in Cdyn and an increase in PVR and P(A-a)O2. This is followed by an increase in Qsp/Qt, PAP, hemoglobin concentration and PCO2. The changes appear related to progressive flooding of the alveolar air space with edema fluid. These findings parallel the sequential cardiorespiratory changes reported to occur in ARDS.

Cardiopulmonary response to sodium fluoride infusion in the dog.

Because humans are occasionally acutely exposed to high levels of fluoride (F-), and cardiac and especially pulmonary tissue accumulate higher concentrations of F- than do the other soft tissues, the present study was undertaken to investigate the effects of acute exposure to toxic plasma levels of F- on cardiopulmonary hemodynamics. Anesthetized dogs were instrumented with right and left cardiac catheters to measure pulmonary arterial and wedge pressures, left ventricular and aortic pressures, left ventricular dP/dt, and cardiac output. An intravenous loading dose of NaF followed by a 3-h infusion produced a plasma F- level of 800 microM in the "low" group of 6 animals, and 1300 microM in the "high" group. The mean pulmonary arterial pressure peaked at 1 h, 83% above preinfusion values in the high group, while that of the low group attained the same level by the end of the infusion period. Impaired pulmonary gas exchange, as indicated by an increased alveolar-arterial PO2 gradient, occurred in half the animals, and an obvious hyperventilation was reflected in a decreased PCO2 value; there was no change in arterial pH, ECG T-wave peaking was common. The central venous pressure declined steadily, while there were no significant changes from controls in systemic arterial pressure, heart rate, cardiac output, or myocardial contractility (dP/dt). Thus, pulmonary hemodynamics and the systemic capacitance vessels are more affected by acute exposure to F- than is cardiac function.

Blood gas measurements.

pH and blood gas measurements are used to detect and monitor ventilation, oxygenation, and acid-base disturbances. The blood sample must be drawn anaerobically and transported in ice water to the laboratory. Partial pressure of carbon dioxide in arterial blood (PaCO2) reflects alveolar ventilation; partial pressure of oxygen in arterial blood (PaO2) reflects oxygen loading. The alveolar-arterial PO2 gradient (PA-aO2) distinguishes hypoxemia due to hypoventilation from that due to inefficent pulmonary gas exchange. The demand status of the cardiovascular system and the hemoglobin value reflect oxygen delivery to tissues. The relationship among pH, PaCO2, and bicarbonate concentration, when interpreted in the light of clinical findings, specifies the type and duration of acid-base disturbance.

Aminophylline Therapy for Idiopathic Apnea in Premature Infants: Effects on Lung Function

The effect of aminophylline on lung function was studied in 14 premature infants with apnea (gestational age, 30.2 weeks; birth weight, 1.052 gm). The infants showed compromised pulmonary function with a large difference in alveolar-arterial PO2 gradient (83.9 mm Hg), a low normal lung compliance of 1.1 ml/cm H2O . kg, and a normal inspiratory resistance of 45.3 cm H2O/liter/sec. Aminophylline therapy did not change these functions significantly, but it decreased the incidence of apneic episodes from 29.7 to 4.4 per day. The effectiveness of aminophylline in treating apnea in premature infants must be related to its central stimulating effect and not to an improvement in lung function and oxygenation.

Variations in pulmonary gas exchange due to changes in pulmonary artery pressure and flow

Effective gas exchange in the lung is achieved by an adequate matching of ventilation to perfusion. In a normal, erect lung, the distribution of ventilation and perfusion is such that several alveolar-capillary units can be observed. At the apex of the lung, alveoli that are hyperventilated with respect to their perfusion can be found. These alveolar-capillary units contribute to an arterial-alveolar Pco, difference, and their magnitude can be assessed by a calculation of the alveolar dead space to alveolar tidal volume ratio. At the bottom of the erect lung, alveoli that are hyperperfused with respect to their ventilation are present, and they contribute to decrease the arterial oxygen tension, and to generate an alveolararterial PO2 gradient. Their magnitude can be calculated by the venous admixture, or shunt equation. Anatomical arteriovenous shunts in the pulmonary circulation will affect gas exchange in the same manner. The largest bulk of the alveolar-capillary units show a ventilation that is commensurate with their perfusion. There can be another possible combination of ventilation-to-perfusion relationships, i.e., units with neither ventilation nor perfusion. They would not contribute to either the alveolar dead space to alveolar tidal volume ration, or the venous admixture, and the lung functions as though these units were not present. The effect of alterations in the ventilationto-perfusion relationship upon pulmonary gas exchange have been studied theoretically [9, 17, 181, in experimental animals [7, 13, 15, 23, 25, 281, and in patients [ 1, 3, 4, 8, 12, 16, 191. Less is known, however, concerning the effects of passive hemodynamic changes in the pulmonary circulation upon gas exchange. In previous experiments, we observed a positive, linear relationship between cardiac output and venous admixture in animals under controlled ventilation [7]. In order to provide additional information concerning the specific influence of passive hemodynamic alterations upon pulmonary gas exchange, a series of experiments were performed on isolated, perfused dog lungs.

The Effect of Pre-existing Pulmonary Vascular Disease on the Response to Mechanical Ventilation with PEEP Following Open-heart Surgery

The effects of mechanical ventilation with and without positive end-expiratory pressure (PEEP) on hemodynamic performance and blood-gas exchange were studied in ten patients following open-heart surgery. Ventilation at constant tidal volume (15 ml/kg body weight) with 10 cm H2O PEEP following aortic valve replacement (AVR) IN FIVE PATIENTs without pulmonary vascular disease was associated with the following significant changes: a rise in arterial Po2, a fall in the alveolar-arterial Po2 gradient when Fio2 = 1.0, decreases in calculated Qs/Qt and cardiac index. Using a similar pattern of ventilation following mitral valve replacement (MVR) in patients with elevated pulmonary vascular resistance, we found a significant decrease in cardiac index (but less than in the AVR group), a significant elevation of calculated physiologic deadspace (Vd/Vt) and no change in Qs/Qt. An hour after removal of PEEP, intravascular pressures, blood flow and blood-gas exchange values of all patients with AVR had returned to control levels; patients with MVR had persistently significantly low cardiac indices, while Vd/Vt returned to pre-PEEP values. These findings suggest that evaluation of responses to different ventilation patterns must take into account pre-existing V/Q abnormalities secondary to pulmonary vascular disease, particularly when these are secondary to chronic congestive heart failure. Following AVR, Qs/Qt changed in the same direction as cardiac index (CI) irrespective of ventilatory pattern: CI decreased and rose as CI increased. The authors conclude that with increasing severity of pulmonary vascular disease, changes in airway pressure will have an unpredictable effect on cardiac index unless the level of myocardial competence is taken into account. In the presence of ventricular failure, changes in pleural (and therefore transmural) pressures will be minimal compared with the high filling pressures and exert no influence on stroke volume. Although pulmonary venous hypertension was more pronounded in the MVR than in the AVR group, there was no significant difference between the postoperative values for Qs/Qt (Fio2 = 1.0), a condition probably fostered by marked differences in pre-existing V/Q.

Ventilation Perfusion Relationships Following Correction of Kyphoscoliosis

Lung function was evaluated in 13 patients before and after surgical correction of spinal deformity. Lung volumes were unchanged, physiologic dead space fell from 155 to 90 ml, and minute ventilation fell from 9.22 to 7.67 liters/min. Arterial oxygen tension (P02) rose from 87 to 93 mm Hg at rest and from 80 to 85 mm Hg during exercise. The alveolar-arterial Po2gradient fell from 26 to 20 mm Hg at rest and was unchanged (90 mm Hg) while breathing oxygen. Distribution of ventilation and perfusion, studied with xenon Xe 133, was normal in patients with curves less than 65°. In those with curves exceeding 70°, ventilation in each lung zone was variable. The normal perfusion gradient from upper to lower lung zones was equally reduced both before and after correction.

FACTORS INFLUENCING THE ARTERIAL OXYGEN TENSION DURING ANAESTHESIA WITH ARTIFICIAL VENTILATION

Factors influencing oxygenation of the arterial blood were studied in 26 patients, during routine anaesthesia with artificial ventilation. The mean minute volume was 10 1./min and the arterial Pco2 27 mm Hg. The mean oxygen consumption was 215 ml/min (STPD) and the physiological deadspace 36 per cent of tidal volume (no allowance being made for the volume of the air passages bypassed by the endotracheal tube). At high levels of inspired oxygen concentration, the mean alveolar-arterial Po2 gradient was 145 mm Hg, corresponding to a calculated shunt of 11 per cent. At an alveolar Po2, of 155 mm Hg the gradient was 52 mm Hg, corresponding to a calculated venous admixture of 9 per cent. There was no progressive increase in venous admixture during anaesthesia in patients under the age of 43 but most of the older patients showed falls and their mean change was significant. Attempts were made to reduce the venous admixture by hyperinflation of the lungs. This was successful in some patients, when a pressure of 40 cm H2O was maintained for 40 seconds. Lower pressures, and the use of a sustained expiratory pressure of 5 cm H2O were not effective. Indices of disordered respiratory function found in this study were not significantly different from those in a comparable study of anaesthetized patients breathing spontaneously.